The main objective of this multicenter study is to evaluate the safety and tolerability of AG4263 in patients with rheumatoid arthritis. The study drug, AG2463 is composed of soluble human glycoprotein HLA DR4 (beta 0401) which has been complexed to a synthetic peptide based on the sequence of amino acids 263-275 of human cartilage glycoprotein 39 (Hcgp39). This is a randomized, double-blind, placebo-controlled, dose escalation, safety and tolerability trial. There will be a total of 31 patients enrolled into this study. All patients will be homozygous or heterozygous for the beta 0401 allele. There are three initial cohorts with three patients in each cohort. Two patients will receive the active drug and one will receive the placebo. The first cohort will receive .05 mcg/kg of the study drug; cohort #2 will receive 2.5 mcg/kg and cohort #3 will receive 12.5 mcg/kg. Dose escalation to the next cohort will begin 21 days or more after the third subject in each prior cohort receives the first dose unless prevented by drug-related toxicity. There are two additional cohorts who will receive a higher dose of the drug (cohorts #4 and #5). Cohort #4 will receive 60 mcg/kg and cohort #5 will receive 150 mcg/kg. In these higher dose cohorts, a total of three patients who are not reactive to CDP 263 will be enrolled. In each of these cohorts, two of the three nonreactive subjects and seven of the eight reactive subjects will be randomized to AG4263; one of the three nonreactive subjects and one of the eight reactive subjects in each cohort will be randomized to placebo. CDP 263 is the aforementioned cartilage derived protein to which the investigational drug is complexed.